STTR 608040: Optimization of the UValidate platform to measure genotoxicity associated with current problematic UV chemical blockers Optimization of the UValidate? platform to measure genotoxicity associated with current problematic UV chemical blockers. Project Summary/ Abstract (word count: 375) Over-the-counter active ingredients that block UVA and UVB are required in all sunscreens, as mandated by the FDA. Recently the safety of these active ingredients has come under scrutiny both from a human health and ecological perspective. Yet there is a lack of alternative UV blockers available to manufacturers leaving the public in a precarious position. The objective of this Phase I STTR is to calibrate a novel UV active ingredient testing platform (termed UValidate?) in order to test potential UV chemical blockers for the skin care industry. Specifically, these chemical blockers would be required to reduce or prevent the deleterious effects of UV irradiation in human cells that comprise the bulk of the epidermis, including fibroblasts, keratinocytes, and melanocytes. Biological endpoints that will be measured after sunscreen and UV exposure include: DNA damage associated with oxidative stress, direct UV DNA damage products (CPD/6-4PP), modulation of DNA repair capacity, and mutagenicity. The product would initially (Phase I) be a comprehensive sunscreen active ingredient testing platform, that in Phase II would be further expanded to identify new or repurposed UV-protective compounds for downstream clinical evaluation. Technical milestones that will be completed in Phase I include: 1) Integrating a novel UV DNA damage-detecting protein-probe into the CometChip methodology, 2) Configuring UVR micro-LED technology to provide a novel UV irradiation source adaptable to screening platforms. 3) Developing a data pipeline that is able to autonomously take the large amounts of information accumulated by the UValidate system and transform the data into a compound-specific predictive result. UValidate is designed to complement rather than replace current sunscreen testing regimes by measuring biological endpoints not evaluated by classical UV absorption measurements. Once we have calibrated UValidate by comprehensively investigating the current OTC UV chemical blockers, we will use data-driven learning protocols to develop a system that can make predictive results about new compounds (Phase II) and in the future be expanded to test the combinatory effects of other agents with sunscreen active ingredients, focusing specifically on insect repellents, moisturizers and environmental pollutants. The impact of the platform will be immediate, with data from the current UV chemical blockers becoming part of the non-clinical assessment that will be used by the FDA to assess the future of the compounds in the marketplace.